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Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue

Author

Listed:
  • Masahide Kawatou

    (Center for iPS Cell Research and Application, Kyoto University
    Kyoto University Graduate School of Medicine)

  • Hidetoshi Masumoto

    (Center for iPS Cell Research and Application, Kyoto University
    Kyoto University Graduate School of Medicine)

  • Hiroyuki Fukushima

    (Center for iPS Cell Research and Application, Kyoto University)

  • Gaku Morinaga

    (Center for iPS Cell Research and Application, Kyoto University
    Nippon Boehringer Ingelheim Co., Ltd. Kobe Pharma Research Institute)

  • Ryuzo Sakata

    (Kyoto University Graduate School of Medicine)

  • Takashi Ashihara

    (Shiga University of Medical Science)

  • Jun K. Yamashita

    (Center for iPS Cell Research and Application, Kyoto University)

Abstract

Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus there is an urgent need for development of models to test or predict the drug sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using 3D cardiac tissue sheets (CTSs) that contain a mixture of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We simultaneously monitor the extracellular field potential (EFP) and the contractile movement of the CTSs. Upon treatment with IKr channel blockers, CTSs exhibit tachyarrhythmias with characteristics of TdP, including both a typical polymorphic EFP and meandering spiral wave re-entry. The TdP-like waveform is predominantly observed in CTSs with the cell mixture, indicating that cellular heterogeneity and the multi-layered 3D structure are both essential factors for reproducing TdP-like arrhythmias in vitro. This 3D model could provide the mechanistic detail underlying TdP generation and means for drug discovery and safety tests.

Suggested Citation

  • Masahide Kawatou & Hidetoshi Masumoto & Hiroyuki Fukushima & Gaku Morinaga & Ryuzo Sakata & Takashi Ashihara & Jun K. Yamashita, 2017. "Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01125-y
    DOI: 10.1038/s41467-017-01125-y
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